Insulin resistance is becoming more prevalent in adults with type 1 diabetes (T1D), a condition frequently referred to as "double diabetes." Weight gain, increased insulin needs, and an increased risk of cardiovascular problems might result from this resistance. Since metformin can improve peripheral insulin sensitivity and lower hepatic glucose production, it has been investigated as an adjuvant treatment for type 1 diabetes. According to recent research, metformin may help insulin-resistant persons with type 1 diabetes maintain their weight, reduce their overall daily insulin dosage, and somewhat improve their glycemic profiles.
Adults bearing the combined challenges of autoimmune insulin insufficiency and acquired insulin resistance may benefit from supplementary therapy in terms of long-term results and quality of life if its effects are evaluated. To measure insulin resistance in muscle, liver, and adipose tissue and to discover biochemical and clinical characteristics linked to muscle and liver insulin resistance, this investigation was organized as a cross-sectional study in people with and without type 1 diabetes.
In a baseline-only cross-sectional investigation, the two-step hyperinsulinemic-euglycemic clamp was used to measure insulin resistance in forty persons with type 1 diabetes and twenty adults without the disease. Hepatic, muscular, and adipose (increased non-esterified fatty acids [NEFA]) insulin resistance was seen in individuals with type 1 diabetes.
The effectiveness of metformin 1500 mg (n = 20) against placebo (n = 20) in lowering insulin resistance in persons with type 1 diabetes over a 26-week period was then evaluated in this study. Changes in endogenous glucose production (EGP) during the clamp's low-dose period were the main result. Out of 40 patients with type 1 diabetes, 37 finished the trial.
Metformin and placebo groups did not vary in EGP at 26 weeks (mean difference 0.2 µmol/kg fat-free mass [FFM]/min [95%CI, −0.4 to 0.8 µmol/kgFFM/min]; p = 0.53). Neither group had an increase in hypoglycemia or ketoacidosis events. Overall, the results of this study indicate that metformin may lower insulin dosage through mechanisms unrelated to insulin resistance, but they do not support the use of metformin to lower insulin resistance in persons with type 1 diabetes.
Source:
Snaith, J. R., Olsen, N., Evans, J., Kowalski, G. M., Bruce, C. R., Samocha-Bonet, D., Breit, S. N., Holmes-Walker, D. J., & Greenfield, J. R. (2025). Effect of metformin on insulin resistance in adults with type 1 diabetes: a 26-week randomized double-blind clinical trial. Nature Communications, 16(1), 9884. https://doi.org/10.1038/s41467-025-65951-1
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